Publications by authors named "Peter Van Dam"

129 Publications

Immuno-PET Molecular Imaging of RANKL in Cancer.

Cancers (Basel) 2021 Apr 30;13(9). Epub 2021 Apr 30.

Molecular Imaging Center Antwerp (MICA), Integrated Personalized and Precision Oncology Network (IPPON), Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium.

Purpose: The involvement of RANK/RANKL signaling in the tumor microenvironment (TME) in driving response or resistance to immunotherapy has only very recently been recognized. Current quantification methods of RANKL expression suffer from issues such as sensitivity, variability, and uncertainty on the spatial heterogeneity within the TME, resulting in conflicting reports on its reliability and limited use in clinical practice. Non-invasive molecular imaging using immuno-PET is a promising approach combining superior targeting specificity of monoclonal antibodies (mAb) and spatial, temporal and functional information of PET. Here, we evaluated radiolabeled anti-RANKL mAbs as a non-invasive biomarker of RANKL expression in the TME.

Experimental Design: Anti-human RANKL mAbs (AMG161 and AMG162) were radiolabeled with Zr using the bifunctional chelator DFO in high yield, purity and with intact binding affinity. After assessing the biodistribution in healthy CD-1 nude mice, [Zr]Zr-DFO-AMG162 was selected for further evaluation in ME-180 (RANKL-transduced), UM-SCC-22B (RANKL-positive) and HCT-116 (RANKL-negative) human cancer xenografts to assess the feasibility of in vivo immuno-PET imaging of RANKL.

Results: [Zr]Zr-DFO-AMG162 was selected as the most promising tracer for further validation based on biodistribution experiments. We demonstrated specific accumulation of [Zr]Zr-DFO-AMG162 in RANKL transduced ME-180 xenografts. In UM-SCC-22B xenograft models expressing physiological RANKL levels, [Zr]Zr-DFO-AMG162 imaging detected significantly higher signal compared to control [Zr]Zr-DFO-IgG2 and to RANKL negative HCT-116 xenografts. There was good visual agreement with tumor autoradiography and immunohistochemistry on adjacent slides, confirming these findings.

Conclusions: [Zr]Zr-DFO-AMG162 can detect heterogeneous RANKL expression in the TME of human cancer xenografts, supporting further translation of RANKL immuno-PET to evaluate tumor RANKL distribution in patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13092166DOI Listing
April 2021

Feasibility study of a 3D camera to reduce electrode repositioning errors during longitudinal ECG acquisition.

J Electrocardiol 2021 Mar 24;66:69-76. Epub 2021 Mar 24.

Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; ECG Excellence BV, Nieuwerbrug, the Netherlands. Electronic address:

Introduction: Longitudinal monitoring of sometimes subtle waveform changes of the 12‑lead electrocardiogram (ECG) is complicated by patient-specific and technical factors, such as the inaccuracy of electrode repositioning. This feasibility study uses a 3D camera to reduce electrode repositioning errors, reduce ECG waveform variability and enable detailed longitudinal ECG monitoring.

Methods: Per subject, three clinical ECGs were obtained during routine clinical follow-up. Additionally, two ECGs were recorded guided by two 3D cameras, which were used to capture the precordial electrode locations and direct electrode repositioning. ECG waveforms and parameters were quantitatively compared between 3D camera guided ECGs and clinical ECGs. Euclidian distances between original and repositioned precordial electrodes from 3D guided ECGs were measured.

Results: Twenty subjects (mean age 65.1 ± 8.2 years, 35% females) were included. The ECG waveform variation between routine ECGs was significantly higher compared to 3D guided ECGs, for both the QRS complex (correlation coefficient = 0.90 vs 0.98, p < 0.001) and the STT segment (correlation coefficient = 0.88 vs. 0.96, p < 0.001). QTc interval variation was reduced for 3D camera guided ECGs compared to routine clinical ECGs (5.6 ms vs. 9.6 ms, p = 0.030). The median distance between 3D guided repositioned electrodes was 10.0 [6.4-15.2] mm, and did differ between males and females (p = 0.076).

Conclusions: 3D guided repositioning of precordial electrodes resulted in, a low repositioning error, higher agreement between waveforms of consecutive ECGs and a reduction of QTc variation. These findings suggest that longitudinal monitoring of disease progression using 12‑lead ECG waveforms is feasible in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jelectrocard.2021.03.006DOI Listing
March 2021

Immunoglobin G/total antibody testing for SARS-CoV-2: A prospective cohort study of ambulatory patients and health care workers in two Belgian oncology units comparing three commercial tests.

Eur J Cancer 2021 05 27;148:328-339. Epub 2021 Feb 27.

Multidisciplinary Oncologic Centre Antwerp (MOCA), Antwerp University Hospital, Wilrijkstraat 10, Edegem, B-2650, Belgium; Center for Oncological Research (CORE), Integrated Personalised and Precision Oncology Network (IPPON), University of Antwerp, Universiteitsplein 1, Wilrijk, B-2610, Belgium.

Background: Coronavirus disease (COVID-19) is interfering heavily with the screening, diagnosis and treatment of cancer patients. Better knowledge of the seroprevalence and immune response after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in this population is important to manage them safely during the pandemic.

Methods: 922 cancer patients, 100 non-cancer patients and 94 health care workers (HCW) attending the Multidisciplinary Oncology Unit of Antwerp University Hospital from 24th of March 2020 till 31st of May 2020, and the Oncology Unit of AZ Maria Middelares Hospital, Ghent, from 13th of April 2020 till 31st of May 2020 participated in the study. The Alinity® (A; Abbott) and Liaison® (D; DiaSorin) commercially available assays were used to measure SARS-CoV-2 IgG, while total SARS-CoV-2 Ig was measured by Elecsys® (R; Roche).

Results: In the overall study population IgG/total SARS-CoV-2 antibodies were found in respectively 32/998 (3.2%), 68/1020 (6.7%), 37/1010 (3.7%) and of individuals using the A, D or R test. Forty-six out of 618 (7.4%) persons had a positive SARS-CoV-2 polymerase chain reaction (RT-PCR) test. Seroprevalence in cancer patients (A:2.2%, D:6.2%, R:3.0%), did not significantly differ from that in non-cancer patients (A:1.1%, D:5.6%, R:0.0%), but was lower than the HCW (A:13%, D:12%, R:12%; respectively Fisher's exact test p = 0.00001, p = 0.046, p = 0.0004). A positive SARS-CoV-2 RT-PCR was found in 6.8% of the cancer patients, 2.3% of the non-cancer patients and 28.1% of the HCW (Fisher's exact test p = 0.0004). Correlation between absolute values of the different Ig tests was poor in the cancer population. Dichotomising a positive versus negative test result, the A and R test correlated well (kappa 0.82 p McNemar test = 0.344), while A and D and R and D did not (respectively kappa 0.49 and 0.57; result significantly different p McNemar test = <0.0001 for both). The rate of seroconversion (>75%) and median absolute antibody levels (A: 7.0 versus 4.7; D 74.0 versus 26.6, R: 16.34 versus 7.32; all >P Mann Whitney U test = 0.28) in cancer patients and HCW with a positive RT-PCR at least 7 days earlier did not show any differences. However, none (N = 0/4) of the patients with hematological tumours had seroconversion and absolute antibody levels remained much lower compared to patients with solid tumours (R: 0.1 versus 37.6, p 0.003; D 4.1 versus 158, p 0.008) or HCW (all p < 0.0001).

Conclusion: HCW were at high risk of being infected by SARS-CoV-2 during the first wave of the pandemic. Seroprevalence in cancer patients was low in the study period. Although Ig immune response in cancer patients with solid tumours does not differ from healthy volunteers, patients with hematological tumours have a very poor humoral immune response. This has to be taken into account in future vaccination programmes in this population. SARS-CoV-2 antibody tests have divergent results and seem to have little added value in the management of cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2021.02.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914028PMC
May 2021

Novel CineECG enables anatomical 3D localization and classification of bundle branch blocks.

Europace 2021 Mar;23(Supplement_1):i80-i87

Division Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht 3508 GA, Heidelberglaan 100, Utrecht, The Netherlands.

Aims: Ventricular conduction disorders can induce arrhythmias and impair cardiac function. Bundle branch blocks (BBBs) are diagnosed by 12-lead electrocardiogram (ECG), but discrimination between BBBs and normal tracings can be challenging. CineECG computes the temporo-spatial trajectory of activation waveforms in a 3D heart model from 12-lead ECGs. Recently, in Brugada patients, CineECG has localized the terminal components of ventricular depolarization to right ventricle outflow tract (RVOT), coincident with arrhythmogenic substrate localization detected by epicardial electro-anatomical maps. This abnormality was not found in normal or right BBB (RBBB) patients. This study aimed at exploring whether CineECG can improve the discrimination between left BBB (LBBB)/RBBB, and incomplete RBBB (iRBBB).

Methods And Results: We utilized 500 12-lead ECGs from the online Physionet-XL-PTB-Diagnostic ECG Database with a certified ECG diagnosis. The mean temporo-spatial isochrone trajectory was calculated and projected into the anatomical 3D heart model. We established five CineECG classes: 'Normal', 'iRBBB', 'RBBB', 'LBBB', and 'Undetermined', to which each tracing was allocated. We determined the accuracy of CineECG classification with the gold standard diagnosis. A total of 391 ECGs were analysed (9 ECGs were excluded for noise) and 240/266 were correctly classified as 'normal', 14/17 as 'iRBBB', 55/55 as 'RBBB', 51/51 as 'LBBB', and 31 as 'undetermined'. The terminal mean temporal spatial isochrone contained most information about the BBB localization.

Conclusion: CineECG provided the anatomical localization of different BBBs and accurately differentiated between normal, LBBB and RBBB, and iRBBB. CineECG may aid clinical diagnostic work-up, potentially contributing to the difficult discrimination between normal, iRBBB, and Brugada patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/europace/euaa396DOI Listing
March 2021

Cancer-Associated Fibroblasts as a Common Orchestrator of Therapy Resistance in Lung and Pancreatic Cancer.

Cancers (Basel) 2021 Feb 27;13(5). Epub 2021 Feb 27.

Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, B2610 Antwerp, Belgium.

Cancer arises from mutations accruing within cancer cells, but the tumor microenvironment (TME) is believed to be a major, often neglected, factor involved in therapy resistance and disease progression. Cancer-associated fibroblasts (CAFs) are prominent and key components of the TME in most types of solid tumors. Extensive research over the past decade revealed their ability to modulate cancer metastasis, angiogenesis, tumor mechanics, immunosuppression, and drug access through synthesis and remodeling of the extracellular matrix and production of growth factors. Thus, they are considered to impede the response to current clinical cancer therapies. Therefore, targeting CAFs to counteract these protumorigenic effects, and overcome the resistance to current therapeutic options, is an appealing and emerging strategy. In this review, we discuss how CAFs affect prognosis and response to clinical therapy and provide an overview of novel therapies involving CAF-targeting agents in lung and pancreatic cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13050987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956441PMC
February 2021

Targeting the PD-1 Axis with Pembrolizumab for Recurrent or Metastatic Cancer of the Uterine Cervix: A Brief Update.

Int J Mol Sci 2021 Feb 11;22(4). Epub 2021 Feb 11.

Center for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium.

Even though cervical cancer is partly preventable, it still poses a great public health problem throughout the world. Current therapies have vastly improved the clinical outcomes of cervical cancer patients, but progress in new systemic treatment modalities has been slow in the last years. Especially for patients with advanced disease this is discouraging, as their prognosis remains very poor. The pathogen-induced nature, the considerable mutational load, the involvement of genes regulating the immune response, and the high grade of immune infiltration, suggest that immunotherapy might be a promising strategy to treat cervical cancer. In this literature review, we focus on the use of PD-1 blocking therapy in cervical cancer, pembrolizumab in particular, as it is the only approved immunotherapy for this disease. We discuss why it has great clinical potential, how it opens doors for personalized treatment in cervical cancer, and which trials are aiming to expand its clinical use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22041807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917788PMC
February 2021

The tele-transition of toxicity management in routine oncology care during the severe acute respiratory syndrome (SARS-CoV-2) pandemic.

Br J Cancer 2021 04 9;124(8):1366-1372. Epub 2021 Feb 9.

Department of Oncology, Antwerp University Hospital Antwerp, Antwerp, Belgium.

Background: Telehealth modalities were introduced during the SARS-CoV-2 pandemic to assure continuation of cancer care and maintain social distance.

Methods: This is a retrospective cohort analysis of our telehealth expansion programme. We adapted two existing patient-reported outcome (PRO) telemonitoring tools that register and (self-)manage toxicities to therapy, while screening for SARS-CoV-2-related symptoms. Outpatients from a tertiary cancer centre were enrolled. The adapted PRO interface allowed for uniform registration of SARS-CoV-2-related symptoms and effective triage of patients at home where we also implemented systematic throat washings, when available.

Results: Three hundred and sixty patients registered to the telemonitoring systems from March 13 to May 15, 2020. Four prespecified SARS-CoV-2 alarms resulted in three patients with positive PCR testing. Other Covid-19 symptoms (fever 5× and cough 2×) led to pretreatment triage resulting in 1 seroconversion after initial negative testing. One of the 477 throat washings proved positive.

Conclusions: The rapid adoption of an amended PRO (self-)registrations and toxicity management system was feasible and coordinated screening for Covid-19. Continued clinical cancer care was maintained, with significant decreased waiting time. The systemic screening with throat washings offered no real improvement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41416-020-01235-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039036PMC
April 2021

Big Data and Artificial Intelligence: Opportunities and Threats in Electrophysiology.

Arrhythm Electrophysiol Rev 2020 Nov;9(3):146-154

Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

The combination of big data and artificial intelligence (AI) is having an increasing impact on the field of electrophysiology. Algorithms are created to improve the automated diagnosis of clinical ECGs or ambulatory rhythm devices. Furthermore, the use of AI during invasive electrophysiological studies or combining several diagnostic modalities into AI algorithms to aid diagnostics are being investigated. However, the clinical performance and applicability of created algorithms are yet unknown. In this narrative review, opportunities and threats of AI in the field of electrophysiology are described, mainly focusing on ECGs. Current opportunities are discussed with their potential clinical benefits as well as the challenges. Challenges in data acquisition, model performance, (external) validity, clinical implementation, algorithm interpretation as well as the ethical aspects of AI research are discussed. This article aims to guide clinicians in the evaluation of new AI applications for electrophysiology before their clinical implementation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15420/aer.2020.26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675143PMC
November 2020

The Non-Bone-Related Role of RANK/RANKL Signaling in Cancer.

Adv Exp Med Biol 2020 ;1277:53-62

Multidisciplinary Oncologic Centre Antwerp (MOCA), Antwerp University Hospital, Edegem, Belgium.

RANK ligand (RANKL) is a member of the tumor necrosis factor alpha superfamily of cytokines. It is the only known ligand binding to a membrane receptor named receptor activator of nuclear factor-kappa B (RANK), thereby triggering recruitment of TNF receptor-associated factor (TRAF) adaptor proteins and activation of downstream pathways. RANK/RANKL signaling is controlled by a decoy receptor, osteoprotegerin (OPG), but also has additional more complex levels of regulation. It is crucial for the differentiation of bone-resorbing osteoclasts and is deregulated in disease processes such as osteoporosis and cancer bone metastasis. Cells expressing RANK and RANKL are commonly found in the tumor environment. In many tumor types, the RANK/RANKL pathway is overexpressed, and this is in most cases correlated with poor prognosis. RANK signaling plays an important role in the innate and adaptive immune response, generates regulatory T (Treg) cells, and increases the production of cytokines. It is also involved in chemo resistance in vitro. Recent evidence suggests that RANKL blockade improves the efficacy of anti-CTLA-4 antibodies against solid tumors and experimental metastasis. Therefore, there is increasing interest to use RANKL inhibition as an immunomodulatory strategy in an attempt to make immune-resistant tumor responsive to immune therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-3-030-50224-9_3DOI Listing
January 2021

Central radiology assessment of the randomized phase III open-label OVHIPEC-1 trial in ovarian cancer.

Int J Gynecol Cancer 2020 Dec 12;30(12):1928-1934. Epub 2020 Oct 12.

Department of Gynaecology, Netherlands Cancer Institute, Amsterdam, The Netherlands

Introduction: Hyperthermic intraperitoneal chemotherapy (HIPEC) improved investigator-assessed recurrence-free survival and overall survival in patients with stage III ovarian cancer in the phase III OVHIPEC-1 trial. We analyzed whether an open-label design affected the results of the trial by central blinded assessment of recurrence-free survival, and tested whether HIPEC specifically targets the peritoneal surface by analyzing the site of disease recurrence.

Methods: OVHIPEC-1 was an open-label, multicenter, phase III trial that randomized 245 patients after three cycles of neoadjuvant chemotherapy to interval cytoreduction with or without HIPEC using cisplatin (100 mg/m). Patients received three additional cycles of chemotherapy after surgery. Computed tomography (CT) scans and serum cancer antigen 125 (CA125) measurements were performed during chemotherapy, and during follow-up. Two expert radiologists reviewed all available CT scans. They were blinded for treatment allocation and clinical outcome. Central revision included Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 measurements and peritoneal cancer index scorings at baseline, during treatment, and during follow-up. Time to centrally-revised recurrence was compared between study arms using Cox proportional hazard models. Subdistribution models compared time to peritoneal recurrence between arms, accounting for competing risks.

Results: CT scans for central revision were available for 231 patients (94%) during neoadjuvant treatment and 212 patients (87%) during follow-up. Centrally-assessed median recurrence-free survival was 9.9 months in the surgery group and 13.2 months in the surgery+HIPEC group (HR for disease recurrence or death 0.72, 95% CI 0.55 to 0.94; p=0.015). The improved recurrence-free survival and overall survival associated with HIPEC were irrespective of response to neoadjuvant chemotherapy and baseline peritoneal cancer index. Cumulative incidence of peritoneal recurrence was lower after surgery+HIPEC, but there was no difference in extraperitoneal recurrences.

Conclusion: Centrally-assessed recurrence-free survival analysis confirms the benefit of adding HIPEC to interval cytoreductive surgery in patients with stage III ovarian cancer, with fewer peritoneal recurrences. These results rule out radiological bias caused by the open-label nature of the study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/ijgc-2020-001825DOI Listing
December 2020

High mortality of cancer patients in times of SARS-CoV-2: Do not generalize!

Eur J Cancer 2020 10 10;138:225-227. Epub 2020 Aug 10.

Multidisciplinary Oncologic Centre Antwerp (MOCA), Antwerp University Hospital, Wilrijkstraat 10, Edegem, B-2650, Belgium; Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Universiteitsplein 1, Wilrijk, B-2610, Belgium.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2020.07.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416784PMC
October 2020

The immunologic aspects in hormone receptor positive breast cancer.

Cancer Treat Res Commun 2020 29;25:100207. Epub 2020 Aug 29.

Multidisciplinary Oncologic Centre Antwerp [(MOCA)], Antwerp University Hospital, Edegem, Belgium; Center for Oncological Research (CORE), University of Antwerp, Wilrijk, Belgium.

Background: Although hormone receptor positive/HER2-negative (HR +/HER2-) breast cancer is the most diagnosed breast cancer type, the immunologic aspects HR positive breast cancer (BC) has been neglected until recently.  The purpose of this paper is to review the current knowledge of the immune environment in HR positive BC and the potential use of immunotherapy in these patients.

Method: A computer-based literature research was carried out using PubMed, American Society of Clinical Oncology Annual Meeting (ASCO) and San Antonio Breast Cancer Symposium (SABCS).

Results: The tumour microenvironment (TME), with infiltrating immune cells, plays an important role in HR positive BC. However, the effects of these immune cells are different in the luminal cancers compared to the other breast cancer types. Even though PD-1 and PD-L1 are less expressed in HR positive BC, pathological complete response (pCR) was more often seen after PD-1 inhibitor treatment in patients with an increased expression. The studies support the assertion that endocrine therapy has immunomodulatory effect.

Conclusion: The reviewed literature indicates that immune cells play an important role in HR positive BC. Considerably more research is needed to determine the real effect of the TME in this patient group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ctarc.2020.100207DOI Listing
August 2020

Oncological outcome, postoperative complications, and mammographic changes after intraoperative radiotherapy with electrons (IOERT) as a boost in a large single-institution cohort of breast cancer patients.

Breast J 2020 10 11;26(10):1937-1945. Epub 2020 Aug 11.

Department of Radiation Oncology, Iridium Kankernetwerk, Antwerp, Belgium.

Advantages of using intraoperative radiotherapy with electrons (IOERT) as a boosting modality in breast-conserving therapy include the direct visualization of the tumor bed, a reduced skin dose, and patient convenience. We report oncological outcome, postoperative complication rate, and mammographic changes on follow-up imaging in women treated at our institution with IOERT as a boost modality in breast-conserving therapy for early-stage breast carcinoma. Between January 2007 and June 2018, 763 consecutive patients were enrolled. During breast-conserving surgery, an IOERT boost of 9 Gy was applied, followed by whole breast irradiation (WBI). At a median follow-up of 62.2 months (range: 0.5-135), 13 in-breast recurrences were observed, yielding a local tumor control rate of 98.4% at 5 years. In multivariable analysis, high tumor grading was predictive for local recurrence (HR = 5.6; 95%CI: 1.19-26.2). A total of 27 (3.5%) patients developed any kind of postoperative complication. None of the tumor characteristics nor any of the IOERT technical parameters were predictive for development of a postoperative complication. On follow-up imaging, 145 patients with mammographic changes BIRADS score ≥3 were found of which 50.3% required a biopsy. Only 17 patients had positive biopsies; none of the IOERT parameters were predictive for false-positive imaging. A 9 Gy IOERT boost combined with postoperative WBI provided outstanding local control rates, was well-tolerated, with limited postoperative complications. However, radiologists must be aware of a presumable higher prevalence of mammographic changes after IORT as a boost.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tbj.13986DOI Listing
October 2020

Novel CineECG Derived From Standard 12-Lead ECG Enables Right Ventricle Outflow Tract Localization of Electrical Substrate in Patients With Brugada Syndrome.

Circ Arrhythm Electrophysiol 2020 09 28;13(9):e008524. Epub 2020 Jul 28.

Department of Arrhythmology and Electrophysiology, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy (E.T.L., G.C., V.B., V.S., G.V., M.M.M., E.M., L.G., V.M., Z.C., L.A, C.P.).

Background: In Brugada syndrome (BrS), diagnosed in presence of a spontaneous or ajmaline-induced type-1 pattern, ventricular arrhythmias originate from the right ventricle outflow tract (RVOT). We developed a novel CineECG method, obtained by inverse electrocardiogram (ECG) from standard 12-lead ECG, to localize the electrical activity pathway in patients with BrS.

Methods: The CineECG enabled the temporospatial localization of the ECG waveforms, deriving the mean temporospatial isochrone from standard 12-lead ECG. The study sample included (1) 15 patients with spontaneous type-1 Brugada pattern, and (2) 18 patients with ajmaline-induced BrS (at baseline and after ajmaline), in whom epicardial potential duration maps were available; (3) 17 type-3 BrS pattern patients not showing type-1 BrS pattern after ajmaline (ajmaline-negative); (4) 47 normal subjects; (5) 18 patients with right bundle branch block (RBBB). According to CineECG algorithm, each ECG was classified as Normal, Brugada, RBBB, or Undetermined.

Results: In patients with spontaneous or ajmaline-induced BrS, CineECG localized the terminal mean temporospatial isochrone forces in the RVOT, congruent with the arrhythmogenic substrate location detected by epicardial potential duration maps. The RVOT location was never observed in normal, RBBB, or ajmaline-negative patients. In most patients with ajmaline-induced BrS (78%), the RVOT location was already evident at baseline. The CineECG classified all normal subjects and ajmaline-negative patients at baseline as Normal or Undetermined, all patients with RBBB as RBBB, whereas all patients with spontaneous and ajmaline-induced BrS as Brugada. Compared with standard 12-lead ECG, CineECG at baseline had a 100% positive predictive value and 81% negative predictive value in predicting ajmaline test results.

Conclusions: In patients with spontaneous and ajmaline-induced BrS, the CineECG localized the late QRS activity in the RVOT, a phenomenon never observed in normal, RBBB, or ajmaline-negative patients. The possibility to identify the RVOT as the location of the arrhythmogenic substrate by the noninvasive CineECG, based on the standard 12-lead ECG, opens new prospective for diagnosing patients with BrS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCEP.120.008524DOI Listing
September 2020

SARS-CoV-2 and cancer: Are they really partners in crime?

Cancer Treat Rev 2020 Sep 11;89:102068. Epub 2020 Jul 11.

Multidisciplinary Oncologic Centre Antwerp (MOCA), Antwerp University Hospital, Wilrijkstraat 10, Edegem B-2650, Belgium; Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Universiteitsplein 1, Wilrijk B-2610, Belgium.

The outbreak of the SARS-CoV-2 pandemic has overwhelmed health care systems in many countries. The clinical presentation of the SARS-CoV-2 varies between a subclinical or flu-like syndrome to that of severe pneumonia with multi-organ failure and death. Initial reports have suggested that cancer patients may have a higher susceptibility to get infected by the SARS-CoV-2 virus but current evidence remains poor as it is biased by important confounders. Patients with ongoing or recent cancer treatment for advanced active disease, metastatic solid tumors and hematological malignancies are at higher risk of developing severe COVID-19 respiratory disease that requires hospitalization and have a poorer disease outcome compared to individuals without cancer. However it is not clear whether these are independent risk factors, or mainly driven by male gender, age, obesity, performance status, uncontrolled diabetes, cardiovascular disease and various other medical conditions. These often have a greater influence on the probability to die due to SARS-CoV-2 then cancer. Delayed diagnosis and suboptimal cancer management due to the pandemic results in disease upstaging and has considerable impact cancer on specific death rates. Surgery during the peak of the pandemic seems to increase mortality, but there is no convincing evidence that adjuvant systemic cancer therapy and radiotherapy are contraindicated, implicating that cancer treatment can be provided safely after individual risk/benefit assessment and some adaptive measures. Underlying immunosuppression, elevated cytokine levels, altered expression of the angiotensin converting enzyme (ACE-2) and TMPRSS2, and a prothrombotic status may fuel the effects of a SARS-CoV-2 in some cancer patients, but have the potential to be used as biomarkers for severe disease and therapeutic targets. The rapidly expanding literature on COVID-19 should be interpreted with care as it is often hampered by methodological and statistical flaws.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ctrv.2020.102068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351667PMC
September 2020

Effect of QRS area reduction and myocardial scar on the hemodynamic response to cardiac resynchronization therapy.

Heart Rhythm 2020 12 24;17(12):2046-2055. Epub 2020 Jul 24.

Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham, United Kingdom. Electronic address:

Background: Vectorcardiographic QRS area (QRS) predicts clinical outcomes after cardiac resynchronization therapy (CRT). Myocardial scar adversely affects clinical outcomes after CRT.

Objective: The purpose of this study in patients with an ideally deployed quadripolar left ventricular (LV) lead (QUAD) was to determine whether reducing QRS leads to an acute hemodynamic response (AHR) and whether scar affects this interaction.

Methods: Patients (n = 26; age 69.2 ± 9.12 years [mean ± SD]) underwent assessment of the maximum rate of change of LV pressure (ΔLV dP/dt) during CRT using various left ventricular pacing locations (LVPLs). Cardiac magnetic resonance (CMR) scan was used to localize LV myocardial scar.

Results: Interindividually, ΔQRS (area under the receiver operating characteristic curve [AUC] 0.81; P <.001) and change in QRS duration (ΔQRSd) (AUC 0.76; P <.001) predicted ΔLV dP/dt after CRT. Scar burden correlated with ΔQRS (r = 0.35; P = .003), ΔQRS (r = 0.35; P = .003), and ΔQRSd (r = 0.46; P <.001). A reduction in QRS was observed with LVPLs remote from scar (-3.28 ± 38.1 μVs) or in LVPLs in patients with no scar at all (-43.8 ± 36.8 μVs), whereas LVPLs over scar increased QRS (22.2 ± 58.4 μVs) (P <.001 for all comparisons). LVPLs within 1 scarred LV segment were associated with lower ΔLV dP/dt (-2.21% ± 11.5%) than LVPLs remote from scar (5.23% ± 10.3%; P <.001) or LVPLs in patients with no scar at all (10.2% ± 7.75%) (both P <.001).

Conclusion: Reducing QRS improves the AHR to CRT. Myocardial scar adversely affects ΔQRS and the AHR. These findings may support the use of ΔQRS and CMR in optimizing CRT using QUAD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hrthm.2020.07.025DOI Listing
December 2020

Acceptability of quality indicators for the management of endometrial, cervical and ovarian cancer: results of an online survey.

BMC Womens Health 2020 07 23;20(1):151. Epub 2020 Jul 23.

Multidisciplinary Oncologic Centre Antwerp (MOCA), Antwerp University Hospital, Wilrijkstraat 10, B2650, Edegem, Belgium.

Background: Measuring quality indicators (QI's) is a tool to improve the quality of care. The aim of this study was to evaluate the acceptability of 36 QI's, defined after a literature search for the management of endometrial, cervical and ovarian cancer. Relevant specialists in the field of interest were surveyed.

Methods: To quantify the opinions of these specialists, an online survey was sent out via mailing to members of gynaecological or oncological societies. The relevance of each QI was questioned on a scale from one to five (1 = irrelevant, 2 = less relevant, 3 = no opinion/neutral, 4 = relevant, 5 = very relevant). If a QI received a score of 4 or 5 in 65% or more of the answers, we state that the respondents consider this QI to be sufficiently relevant to use in daily practice.

Results: The survey was visited 238 times and resulted in 53 complete responses (29 Belgian, 24 other European countries). The majority of the specialists were gynaecologists (45%). Five of the 36 QI's (13,9%) did not reach the cut-off of 65%: referral to a tertiary center, preoperative staging of endometrial cancer by MRI, preoperative staging of cervical cancer by positron-emission tomography, incorporation of intracavitary brachytherapy in the treatment of cervical cancer, reporting ASA and WHO score for each patient. After removing the 5 QI's that were not considered as relevant by the specialists and 3 additional 3 QI's that we were considered to be superfluous, we obtained an optimized QI list.

Conclusion: As QI's gain importance in gynecological oncology, their use can only be of value if they are universally interpreted in the same manner. We propose an optimized list of 28 QI's for the management of endometrial, cervical and ovarian cancer which responders of our survey found relevant. Further validation is needed to finalize and define a set of QI's that can be used in future studies, audits and benchmarking.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12905-020-00999-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376904PMC
July 2020

HIPEC in advanced epithelial ovarian cancer: why is there controversy?

Curr Opin Oncol 2020 09;32(5):451-458

Department of Gynecological Oncology, Westmead Hospital.

Purpose Of Review: The randomized OVHIPEC study provided further evidence that adding heated intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery significantly improved recurrence-free and overall survival in stage III epithelial ovarian cancer (EOC) patients, who were ineligible for primary cytoreductive surgery due to extensive intraperitoneal disease. Because opinions have been divided as to whether HIPEC is now a new standard of care for advanced EOC, the pros and cons of this approach are examined. A comparison with the ongoing discussion about the role of intraperitoneal chemotherapy is made.

Recent Findings: For both techniques, experience is crucial and a learning curve essential. Compared with intraperitoneal chemotherapy, intraoperative application of HIPEC provides superior distribution through the peritoneal cavity. HIPEC, as given in OVHIPEC, did not significantly increase adverse events, had no negative effect on quality of life and was cost-effective.

Summary: Despite the ongoing debate about HIPEC, an important first step in attempting to demonstrate the efficacy of HIPEC in the first-line setting has been made with OVHIPEC. Critics have been of value to optimize future trials with HIPEC in patients with EOC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCO.0000000000000659DOI Listing
September 2020

Prescreening for COVID-19 in patients receiving cancer treatment using a patient-reported outcome platform.

ESMO Open 2020 06;5(3):e000817

Department of Medical Oncology, MOCA, University Hospital Antwerp (UZA), Antwerp, Belgium; Department of Molecular Imaging, Pathology, Radiotherapy & Oncology (MIPRO), Center for Oncological Research (CORE), Antwerp University, Antwerp, Belgium.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/esmoopen-2020-000817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307523PMC
June 2020

A video-game based cognitive training for breast cancer survivors with cognitive impairment: A prospective randomized pilot trial.

Breast 2020 Oct 12;53:23-32. Epub 2020 Jun 12.

Multidisciplinary Oncologic Center Antwerp (MOCA), Antwerp University Hospital, Edegem, B2650, Belgium; Centre for Oncological Research (CORE), University of Antwerp, Wilrijk, B2610, Belgium. Electronic address:

Introduction: We investigated whether a web-based cognitive training video game is an effective approach to improve cognitive decline in combination with our standard of care for rehabilitation of breast cancer (BC) patients.

Materials And Methods: Self-selected BC patients between 18 and 71 years old complaining of disturbing cognitive impairment were studied. The patients received access to a web-based internet video game and online cognitive assessments (Aquasnap, Cambridge, MyCQ™). The early intervention group (n = 23) had a training program of 6 months of at least three times a week for a minimum of 60 min of game playing per week at home in addition to standard of care rehabilitation. The delayed intervention (n = 23) received standard of care for three months, followed by three months of similar MyCQ training. Outcome measures were the MyCQ (sub)scores and Activity of Daily Life (ADL), mood, subjective cognition and functional cognitive status measured by classic neuropsychological tests.

Results: At baseline the means for CFQ (a measure of self-reported cognitive failure), anxiety, PSQI and self-reflectiveness were beyond normal range in both groups. CFQ improved significantly better in the intervention group (p = 0.029). Combining the evolution over time in the entire population a significant improvement was seen for overall MyCQ score, level of fear, physical and emotional role limitation, and health change (all p < 0.05), but self-reflectivess deteriorated (p < 0.05)). Significant differences in the various MyCQ subtests over time were: improved speed in choice reaction time, visual memory recognition, N back 1 and 2, coding, trail making test B, improved accuracy of N back 1 and 2 (all p < 0.05).

Conclusion: A program of cognitive training improves cognitive functioning over time. "Aquasnap" has a beneficial effect on the perception of subjective cognitive functioning (CFQ) but the exact role of video gaming in this process remains uncertain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.breast.2020.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375646PMC
October 2020

AMTRA: a multicentered experience of a web-based monitoring and tailored toxicity management system for cancer patients.

Support Care Cancer 2021 Feb 9;29(2):859-867. Epub 2020 Jun 9.

Department of Oncology, Multidisciplinary Oncological Center Antwerp, MOCA, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem, Belgium.

Background: Technology-based interventions are increasingly being introduced in routine clinical cancer care. There is a need for reliable systems to monitor treatment-related toxicity in a standardized manner. Such electronic tools bridge the gap in providing quality home-based monitoring.

Methods: From July 2017 to December 2017, we performed a multicentered, non-randomized prospective cohort analysis with patients who were receiving routine chemotherapy for various solid tumors, using a web-based patient-reported toxicity registration, management, and intervention system called AMTRA (ambulatory Monitoring of cancer Therapy using an interactive Application) linked to the homecare nursing organization Remedus®. Twelve common toxicities plus pain and two biometrics could be registered daily or more frequently as required. These were processed centrally to generate tailored advice for lesser symptoms or a phone call from a dedicated nurse in case of severe or prolonged toxicity. A compliance tool to monitor oral therapies was incorporated in the system.

Results: One hundred sixty-eight patients (92%) were enrolled, with 31,514 registrations analyzed. One hundred eight patients reported severe toxicity (> 1461 registrations), resulting in 102 clinical interventions ranging from self-management advice, supplemental consultations to hospitalizations. Compliance to oral chemotherapy was high using AMTRA with a median of 98.7% (95 confidence interval (CI) [93.5-100.0%]). Seventy-nine percent of patients stated that the availability of AMTRA self-reports was useful in communication with the care provider, while 75% felt more in control while managing their treatment.

Conclusions: The application of an interactive PRO-system in routine symptom management of cancer patients allowed standardized documentation of toxicities and recorded a high compliance with oral treatment. It allows for rapid interaction for toxicities and cancer-related symptoms experienced at home.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00520-020-05550-6DOI Listing
February 2021

The art of obtaining a high yield of cell-free DNA from urine.

PLoS One 2020 6;15(4):e0231058. Epub 2020 Apr 6.

Center for Oncological Research Antwerp (CORE), University of Antwerp (UA), Wilrijk, Belgium.

Although liquid biopsies offer many advantages over tissue biopsies, they are not yet standard practice. An important reason for the lack of implementation is the unavailability of well standardized techniques and guidelines, especially for pre-analytical conditions which are an important factor causing the current sensitivity issues. To overcome these limitations, we investigated the effect of several pre-analytical conditions on the concentration of cell-free DNA (cfDNA) and cellular genomic DNA (gDNA) contamination. Urine samples from healthy volunteers (HVs) and cancer patients were collected and processed according to specific pre-analytical conditions. Our results show that in samples with a relatively small volume more than 50% of the cfDNA can be found in the first 50 mL of the urine sample. The total DNA concentration increased again when samples were collected more than 3.5 hours apart. Adding preservative to urine samples is recommended to obtain high concentrations of cfDNA. To remove the cellular content, high speed centrifugation protocols as 4,000g 10min or 3,000g 15min are ideal for urine collected in cfDNA Urine Preserve (Streck). Although this study was a pilot study and needs to be confirmed in a larger study population, clear trends in the effect of several pre-analytical conditions were observed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231058PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7135229PMC
July 2020

Related mobile pathogenicity chromosomes in Fusarium oxysporum determine host range on cucurbits.

Mol Plant Pathol 2020 06 4;21(6):761-776. Epub 2020 Apr 4.

Molecular Plant Pathology, University of Amsterdam, Amsterdam, Netherlands.

Fusarium oxysporum f. sp. radicis-cucumerinum (Forc) causes severe root rot and wilt in several cucurbit species, including cucumber, melon, and watermelon. Previously, a pathogenicity chromosome, chr , was identified in Forc. Strains that were previously nonpathogenic could infect multiple cucurbit species after obtaining this chromosome via horizontal chromosome transfer (HCT). In contrast, F. oxysporum f. sp. melonis (Fom) can only cause disease on melon plants, even though Fom contains contigs that are largely syntenic with chr . The aim of this study was to identify the genetic basis underlying the difference in host range between Fom and Forc. First, colonization of different cucurbit species between Forc and Fom strains showed that although Fom did not reach the upper part of cucumber or watermelon plants, it did enter the root xylem. Second, to select candidate genomic regions associated with differences in host range, high-quality genome assemblies of Fom001, Fom005, and Forc016 were compared. One of the Fom contigs that is largely syntenic and highly similar in sequence to chr contains the effector gene SIX6. After HCT of the SIX6-containing chromosome from Fom strains to a nonpathogenic strain, the recipient (HCT) strains caused disease on melon plants, but not on cucumber or watermelon plants. These results provide strong evidence that the differences in host range between Fom and Forc are caused by differences between transferred chromosomes of Fom and chr , thus narrowing down the search for genes allowing or preventing infection of cucumber and watermelon to genes located on these chromosomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/mpp.12927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214479PMC
June 2020

A Unified Pipeline for ECG Imaging Testing.

Comput Cardiol (2010) 2019 Sep 24;46. Epub 2020 Feb 24.

University of Utah, Salt Lake City, Utah, USA.

The Consortium for ECG Imaging (CEI) has formed several collaborative projects to evaluate and improve technical aspects of Electrocardiographic Imaging (ECGI), but these efforts are not yet implemented into an integrated software framework. We developed a framework to unify the multiple techniques and stages of ECGI into one pipeline. This framework merges existing open source packages: SCIRun, a problem solving environment; the Forward/Inverse toolkit, a series of SCIRun modules for ECGI; and PFEIFER, a cardiac signal pre-processing tool. The Unified ECGI Toolkit (UETK), combined with the EDGAR dataset, allows users to test and validate a vast array of parameters within each stage of the ECGI pipeline. We expect that this unified tool will help introduce new researchers to ECGI, facilitate interaction between the various groups working on ECGI, and establish a common approach for researchers to test and validate their ECGI techniques.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.22489/cinc.2019.437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083590PMC
September 2019

Inflammatory breast cancer cells are characterized by abrogated TGFβ1-dependent cell motility and SMAD3 activity.

Breast Cancer Res Treat 2020 Apr 10;180(2):385-395. Epub 2020 Feb 10.

Center for Oncological Research (CORE), Faculty of Medicine and Health Sciences - University of Antwerp, Campus Drie Eiken - Universiteitsplein 1, 2610, Wilrijk - Antwerp, Belgium.

Purpose: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer with elevated metastatic potential, characterized by tumor emboli in dermal and parenchymal lymph vessels. This study has investigated the hypothesis that TGFβ signaling is implicated in the molecular biology of IBC.

Methods: TGFβ1-induced cell motility and gene expression patterns were investigated in three IBC and three non-IBC (nIBC) cell lines. Tissue samples from IBC and nIBC patients were investigated for the expression of nuclear SMAD2, SMAD3, and SMAD4. SMAD protein levels were related to gene expression data.

Results: TGFβ1-induced cell motility was strongly abrogated in IBC cells (P = 0.003). Genes differentially expressed between IBC and nIBC cells post TGFβ1 exposure revealed attenuated expression of SMAD3 transcriptional regulators, but overexpression of MYC target genes in IBC. IBC patient samples demonstrated a near absence of SMAD3 and -4 expression in the primary tumor compared to nIBC patient samples (P < 0.001) and a further reduction of staining intensity in tumor emboli. Integration of gene and protein expression data revealed that a substantial fraction of the IBC signature genes correlated with SMAD3 and these genes are indicative of attenuated SMAD3 signaling in IBC.

Conclusion: We demonstrate attenuated SMAD3 transcriptional activity and SMAD protein expression in IBC, together with obliterated TGFβ1-induced IBC cell motility. The further reduction of nuclear SMAD expression levels in tumor emboli suggests that the activity of these transcription factors is involved in the metastatic dissemination of IBC cells, possibly by enabling collective invasion after partial EMT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10549-020-05571-zDOI Listing
April 2020

Man vs machine: Performance of manual vs automated electrocardiogram analysis for predicting the chamber of origin of idiopathic ventricular arrhythmia.

J Cardiovasc Electrophysiol 2020 02 25;31(2):410-416. Epub 2019 Dec 25.

Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Background: Radiofrequency catheter ablation of idiopathic ventricular arrhythmias (VAs) is performed to eliminate symptoms and to prevent or reverse arrhythmia-induced cardiomyopathy. Preprocedural prediction of the chamber of VA origin is critical for patient counseling, procedure planning, and guidance of invasive mapping.

Objective: We aimed to assess the performance of manual expert versus automated 12-lead electrocardiogram (ECG) analysis in the prediction of VA origin.

Methods: Patients with ablation of idiopathic VA and sustained success were included. The VA origin was defined as the site where ablation caused arrhythmia suppression. Standard baseline 12-lead ECGs with documentation of the VA were analyzed manually in a blinded fashion by three electrophysiologists and three electrophysiology (EP) fellows. In addition, the same standard 12-lead ECG was analyzed by an automated computer algorithm using a vectorcardiographic approach.

Results: Thirty-eight patients (median age, 47 [interquartile range, 37-58]; 68% female) were enrolled. The VA originated from the right ventricle in 24 (63%) and the left ventricle in 14 (37%) patients. The electrophysiologists and EP fellows identified the VA chamber of origin with a similar accuracy of 73% and 72% (P = .72). The automated algorithm showed a higher accuracy of 89% (P = .03 compared with electrophysiologists and EP fellows). This resulted in a sensitivity of 95% and specificity of 86%.

Conclusion: While the manual ECG analysis of the standard 12-lead ECG by both electrophysiologists and EP fellows correctly identified the chamber of VA origin in around 75% of cases, an automated vectorcardiographic computer algorithm achieved an accuracy of 89% with clinically acceptable diagnostic parameters.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jce.14320DOI Listing
February 2020

Triple-negative breast cancer-Role of immunology: A systemic review.

Breast J 2020 05 4;26(5):995-999. Epub 2019 Dec 4.

Multidisciplinary Oncologic Centre Antwerp (MOCA), Antwerp University Hospital, Edegem, Belgium.

Recently, the complex role of immune therapy has been the target of increased attention in breast cancer, particularly in triple-negative breast cancer (TNBC). Although TNBC is sensitive to chemotherapy, the recurrence and mortality rates are worse compared with the other breast cancer types. In addition, TNBC still lacks targeted treatment options. With the improved understanding of the immune system in TNBC, it is expected that new predictive and prognostic markers will be identified, and innovative treatment modalities will be developed. The aim of this review was to provide an overview of the effector cells in the TNBC's microenvironment and to highlight a novel approach to treat this kind of cancer. A computer-based literature research was carried out using PubMed, American Society of Clinical Oncology Annual Meeting (ASCO) and San Antonio Breast Cancer Symposium (SABCS). To date, studies have shown that tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) play a very important role in the TNBC's microenvironment. Tumor-infiltrating lymphocytes can even be considered as biomarkers to predict chemotherapy response in TNBC. Furthermore, TNBC was shown to have immune active subtypes, and therefore, the use of immunotherapy may be an attractive treatment approach. In this respect, several randomized studies have been designed or are currently ongoing to explore the combination of chemotherapy with immunotherapy in TNBC. Combination of chemo- and immunotherapy is likely to be beneficial in a subgroup of patients with TNBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tbj.13696DOI Listing
May 2020

Changes in QRS Area and QRS Duration After Cardiac Resynchronization Therapy Predict Cardiac Mortality, Heart Failure Hospitalizations, and Ventricular Arrhythmias.

J Am Heart Assoc 2019 11 28;8(21):e013539. Epub 2019 Oct 28.

Aston Medical Research Institute Aston Medical School Aston University Birmingham United Kingdom.

Background Predicting clinical outcomes after cardiac resynchronization therapy (CRT) and its optimization remain a challenge. We sought to determine whether pre- and postimplantation QRS area (QRS) predict clinical outcomes after CRT. Methods and Results In this retrospective study, QRS, derived from pre- and postimplantation vectorcardiography, were assessed in relation to the primary end point of cardiac mortality after CRT with or without defibrillation. Other end points included total mortality, total mortality or heart failure (HF) hospitalization, total mortality or major adverse cardiac events, and the arrhythmic end point of sudden cardiac death or ventricular arrhythmias with or without a shock. In patients (n=380, age 72.0±12.4 years, 68.7% male) undergoing CRT over 7.7 years (median follow-up: 3.8 years [interquartile range 2.3-5.3]), preimplantation QRS ≥102 μVs predicted cardiac mortality (HR: 0.36; <0.001), independent of QRS duration (QRSd) and morphology (<0.001). A QRS reduction ≥45 μVs after CRT predicted cardiac mortality (HR: 0.19), total mortality (HR: 0.50), total mortality or heart failure hospitalization (HR: 0.44), total mortality or major adverse cardiac events (HR: 0.43) (all <0.001) and the arrhythmic end point (HR: 0.26; <0.001). A concomitant reduction in QRS and QRSd was associated with the lowest risk of cardiac mortality and the arrhythmic end point (both HR: 0.12, <0.001). Conclusions Pre-implantation QRS, derived from vectorcardiography, was superior to QRSd and QRS morphology in predicting cardiac mortality after CRT. A postimplant reduction in both QRS and QRSd was associated with the best outcomes, including the arrhythmic end point.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.119.013539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6898809PMC
November 2019

Effect of Segmentation Variation on ECG Imaging.

Comput Cardiol (2010) 2018 Sep;45

University of Utah, Salt Lake City, Utah, USA.

ECG imaging (ECGI) is the process of calculating electrical cardiac activity from body surface recordings from the geometry and conductivity of the torso volume. A key first step to create geometric models for ECGI and a possible source of considerable variability is to segment the surface of the heart. We hypothesize that this variation in cardiac segmentation will produce variation in the computed ventricular surface potentials from ECGI. To evaluate this hypothesis, we leveraged the resources of the Consortium for ECG Imaging (CEI) to carry out a comparison of ECGI results from the same body surface potentials and multiple ventricular segmentations. We found that using the different segmentations produced variability in the computed ventricular surface potentials. Not surprisingly, locations of greater variance in the computed potential correlated to locations of greater variance in the segmentations, for example near the pulmonary artery and basal anterior left ventricular wall. Our results indicate that ECGI may be more sensitive to segmentation errors on the anterior epicardial surface than on other areas of the heart.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.22489/CinC.2018.374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800733PMC
September 2018

The potential and controversy of targeting STAT family members in cancer.

Semin Cancer Biol 2020 02 9;60:41-56. Epub 2019 Oct 9.

Multidisciplinary Oncologic Centre Antwerp (MOCA), Antwerp University Hospital, Wilrijkstraat 10, Edegem, B-2650, Belgium; Center for Oncological Research (CORE), University of Antwerp, Universiteitsplein 1, Wilrijk, B-2610, Belgium; Gynaecologic Oncology Unit, Antwerp University Hospital, Wilrijkstraat 10, Edegem, B-2650, Belgium. Electronic address:

The Signal Transducer and Activator of Transcription (STAT) family of proteins consists of transcription factors that play a complex and essential role in the regulation of physiologic cell processes, such as proliferation, differentiation, apoptosis and angiogenesis, and serves to organize the epigenetic landscape of immune cells. To date, seven STAT genes have been identified in the human genome; STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6. They all account for diverse effects in response to extracellular signaling proteins, mainly by altering gene transcription in the effector cells. Members of the STAT family have been implicated in human cancer development, progression, metastasis, survival and resistance to treatment. Particularly STAT3 and STAT5 are of interest in cancer biology. They are currently considered as oncogenes, but their signaling is embedded into a complex and delicate balance between different (counteracting) transcription factors, and thus, in some contexts they can have a tumor suppressive role. Assessing STAT signaling mutations as well as screening for aberrant STAT pathway activation may have a role to predict sensitivity to immunotherapy and targeted STAT inhibition. In the present comprehensive review of the literature, we discuss in-depth the role of each STAT family member in cancer, assemble cutting-edge information on the use of these molecules as potential biomarkers and targets for treatment, and address why their clinical implementation is controversy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.semcancer.2019.10.002DOI Listing
February 2020